Skip to main content
Erschienen in: Acta Diabetologica 6/2018

15.03.2018 | Original Article

Urine levels of 5-aminoimidazole-4-carboxamide riboside (AICAR) in patients with type 2 diabetes

verfasst von: Michael Mendler, Stefan Kopf, Jan B. Groener, Christin Riedinger, Thomas H. Fleming, Peter P. Nawroth, Jürgen G. Okun

Erschienen in: Acta Diabetologica | Ausgabe 6/2018

Einloggen, um Zugang zu erhalten

Abstract

Aims

5-Aminoimidazole-4-carboxamide riboside (AICAR) is an endogenous activator of AMPK, a central regulator of energy homeostasis. Loss and/or reduction of AMPK signaling plays an important role in the development of insulin resistance in type 2 diabetes. The loss of AMPK in diabetes could be due to a loss of AICAR. The aim of this study was to characterize urine levels of AICAR in diabetes and determine whether an association exists with respect to late complications, e.g., retinopathy, nephropathy and neuropathy.

Methods

Urine AICAR was measured by liquid chromatography tandem mass spectrometry in 223 patients consisting of 5 healthy controls, 63 patients with pre-diabetes, 29 patients with newly diagnosed type 2 diabetes and 126 patients with long-standing type 2 diabetes. For statistical analyses, nonparametric Kruskal–Wallis test, one-way ANOVA and multivariate regression analysis were performed to investigate the associations of urinary AICAR excretion within different groups and different clinical parameters.

Results

The mean urine AICAR for all 223 patients was 694.7 ± 641.1 ng/ml. There was no significant difference in urine AICAR between the control and patients with diabetes (592.3 ± 345.1 vs. 697.1 ± 646.5 ng/ml). No association between any of the biochemical and/or clinical parameters measured and urine AICAR was found, with the exception of age of patient (R = − 0.34; p < 0.01) and estimated glomerular filtration rate (R = 0.19; p = 0.039). These results were confirmed additionally by linear regression analysis.

Conclusions

Clinical diabetes is not associated with a change in endogenous AICAR levels. Loss of AICAR may therefore not be a mechanism by which AMPK signaling is reduced in diabetes.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
3.
Zurück zum Zitat Bandyopadhyay GK, Yu JG, Ofrecio J, Olefsky JM (2006) Increased malonyl-CoA levels in muscle from obese and type 2 diabetic subjects lead to decreased fatty acid oxidation and increased lipogenesis; thiazolidinedione treatment reverses these defects. Diabetes 55(8):2277–2285. https://doi.org/10.2337/db06-0062 CrossRefPubMed Bandyopadhyay GK, Yu JG, Ofrecio J, Olefsky JM (2006) Increased malonyl-CoA levels in muscle from obese and type 2 diabetic subjects lead to decreased fatty acid oxidation and increased lipogenesis; thiazolidinedione treatment reverses these defects. Diabetes 55(8):2277–2285. https://​doi.​org/​10.​2337/​db06-0062 CrossRefPubMed
5.
Zurück zum Zitat Corton JM, Gillespie JG, Hawley SA, Hardie DG (1995) 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur J Biochem 229(2):558–565CrossRefPubMed Corton JM, Gillespie JG, Hawley SA, Hardie DG (1995) 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur J Biochem 229(2):558–565CrossRefPubMed
6.
Zurück zum Zitat Sullivan JE, Carey F, Carling D, Beri RK (1994) Characterisation of 5′-AMP-activated protein kinase in human liver using specific peptide substrates and the effects of 5′-AMP analogues on enzyme activity. Biochem Biophys Res Commun 200(3):1551–1556CrossRefPubMed Sullivan JE, Carey F, Carling D, Beri RK (1994) Characterisation of 5′-AMP-activated protein kinase in human liver using specific peptide substrates and the effects of 5′-AMP analogues on enzyme activity. Biochem Biophys Res Commun 200(3):1551–1556CrossRefPubMed
7.
Zurück zum Zitat Davies SP, Helps NR, Cohen PT, Hardie DG (1995) 5′-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2AC. FEBS Lett 377(3):421–425. https://doi.org/10.1016/0014-5793(95)01368-7 CrossRefPubMed Davies SP, Helps NR, Cohen PT, Hardie DG (1995) 5′-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2AC. FEBS Lett 377(3):421–425. https://​doi.​org/​10.​1016/​0014-5793(95)01368-7 CrossRefPubMed
8.
Zurück zum Zitat Hawley SA, Selbert MA, Goldstein EG, Edelman AM, Carling D, Hardie DG (1995) 5′-AMP activates the AMP-activated protein kinase cascade, and Ca2+/calmodulin activates the calmodulin-dependent protein kinase I cascade, via three independent mechanisms. J Biol Chem 270(45):27186–27191CrossRefPubMed Hawley SA, Selbert MA, Goldstein EG, Edelman AM, Carling D, Hardie DG (1995) 5′-AMP activates the AMP-activated protein kinase cascade, and Ca2+/calmodulin activates the calmodulin-dependent protein kinase I cascade, via three independent mechanisms. J Biol Chem 270(45):27186–27191CrossRefPubMed
10.
Zurück zum Zitat Bergeron R, Previs SF, Cline GW et al (2001) Effect of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats. Diabetes 50(5):1076–1082CrossRefPubMed Bergeron R, Previs SF, Cline GW et al (2001) Effect of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats. Diabetes 50(5):1076–1082CrossRefPubMed
11.
Zurück zum Zitat Buhl ES, Jessen N, Schmitz O et al (2001) Chronic treatment with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside increases insulin-stimulated glucose uptake and GLUT4 translocation in rat skeletal muscles in a fiber type-specific manner. Diabetes 50(1):12–17CrossRefPubMed Buhl ES, Jessen N, Schmitz O et al (2001) Chronic treatment with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside increases insulin-stimulated glucose uptake and GLUT4 translocation in rat skeletal muscles in a fiber type-specific manner. Diabetes 50(1):12–17CrossRefPubMed
12.
Zurück zum Zitat Iglesias MA, Ye JM, Frangioudakis G et al (2002) AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats. Diabetes 51(10):2886–2894CrossRefPubMed Iglesias MA, Ye JM, Frangioudakis G et al (2002) AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats. Diabetes 51(10):2886–2894CrossRefPubMed
20.
Zurück zum Zitat Lulenski G, Donaldson M, Newcombe D (1970) Urinary aminoimidazolecarboxamide levels in children with acute leukemia. Pediatrics 45(6):983–995PubMed Lulenski G, Donaldson M, Newcombe D (1970) Urinary aminoimidazolecarboxamide levels in children with acute leukemia. Pediatrics 45(6):983–995PubMed
21.
Zurück zum Zitat Newcombe DS (1970) The urinary excretion of aminoimidazolecarboxamide in the Lesch–Nyhan syndrome. Pediatrics 46(4):508–512PubMed Newcombe DS (1970) The urinary excretion of aminoimidazolecarboxamide in the Lesch–Nyhan syndrome. Pediatrics 46(4):508–512PubMed
22.
Zurück zum Zitat Sweetman L, Nyhan WL (1970) Detailed comparison of the urinary excretion of purines in a patient with the Lesch–Nyhan syndrome and a control subject. Biochem Med 4(2):121–134CrossRefPubMed Sweetman L, Nyhan WL (1970) Detailed comparison of the urinary excretion of purines in a patient with the Lesch–Nyhan syndrome and a control subject. Biochem Med 4(2):121–134CrossRefPubMed
24.
Zurück zum Zitat Pokrywka A, Cholbinski P, Kaliszewski P, Kowalczyk K, Konczak D, Zembron-Lacny A (2014) Metabolic modulators of the exercise response: doping control analysis of an agonist of the peroxisome proliferator-activated receptor delta (GW501516) and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). J Physiol Pharmacol 65(4):469–476PubMed Pokrywka A, Cholbinski P, Kaliszewski P, Kowalczyk K, Konczak D, Zembron-Lacny A (2014) Metabolic modulators of the exercise response: doping control analysis of an agonist of the peroxisome proliferator-activated receptor delta (GW501516) and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). J Physiol Pharmacol 65(4):469–476PubMed
31.
Zurück zum Zitat Henry RJ (1964) Non-protein nitrogenous constituents. In: Henry RJ (ed) Clinical chemistry, principles and techniques. Harper & Row, New York, pp 292–299 Henry RJ (1964) Non-protein nitrogenous constituents. In: Henry RJ (ed) Clinical chemistry, principles and techniques. Harper & Row, New York, pp 292–299
35.
Zurück zum Zitat Vincent MF, Marangos PJ, Gruber HE, Van den Berghe G (1991) Inhibition by AICA riboside of gluconeogenesis in isolated rat hepatocytes. Diabetes 40(10):1259–1266CrossRefPubMed Vincent MF, Marangos PJ, Gruber HE, Van den Berghe G (1991) Inhibition by AICA riboside of gluconeogenesis in isolated rat hepatocytes. Diabetes 40(10):1259–1266CrossRefPubMed
Metadaten
Titel
Urine levels of 5-aminoimidazole-4-carboxamide riboside (AICAR) in patients with type 2 diabetes
verfasst von
Michael Mendler
Stefan Kopf
Jan B. Groener
Christin Riedinger
Thomas H. Fleming
Peter P. Nawroth
Jürgen G. Okun
Publikationsdatum
15.03.2018
Verlag
Springer Milan
Erschienen in
Acta Diabetologica / Ausgabe 6/2018
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-018-1130-2

Weitere Artikel der Ausgabe 6/2018

Acta Diabetologica 6/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.